rs1554082512
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_205836.3(FBXO38):c.2755G>A(p.Val919Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_205836.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBXO38 | NM_205836.3 | c.2755G>A | p.Val919Ile | missense_variant, splice_region_variant | Exon 17 of 22 | ENST00000340253.10 | NP_995308.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 28
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Distal hereditary motor neuropathy type 2 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in one or more individuals who were not affected with FBXO38-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 541012). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 844 of the FBXO38 protein (p.Val844Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at